Characterization of th components of lysates of Limulus amebocytes which react with bacterial endotoxin will be continued to determine the nature of the reaction between bacterial endotoxin and this invertebrate coagulation sytem. Additional purification of the clottable protein will be attempted. Granules of Limulus amebocytes will be isolated and their contents analyzed. The effects of fibrinogen-fibrin degradation products on hepatic synthesis of fibrinogen will be measured. The manner in which Arvin converts fibrinogen to fibrin, and the specificity of this reaction, in vivo, will be studied. Anticoagulation produced by Arvin will be evaluated clinically during the use of membrane oxygenators and renal dialysis. Inhibition of the reaction between thrombin and fibrinogen by cyanate will be investigated. The use of isotopically labelled activators of plasminogen will be evaluated as a means of detecting thrombus formation in vivo. Studies of thromocytosis, certain inherited hemorrhagic disorders including hemophilia A and von Willebrand's disease, chronic immunologic thrombocytopenic purpura, and disseminated intravascular coagulation will be carried out to provide undestanding of the pathophysiological mechanisms which result in hemorrhage and thrombosis, and bases for their rational treatment.